DESCRIPTION: (Adapted from applicant's description) This revised application proposes Rita Suri, M.D. for a K23 Mentored Patient-Oriented Research Career Development Award for the study of depressive disorders during pregnancy. A limited body of knowledge regarding the impact of mood state on the fetus complicates the management of major depression during pregnancy. The purpose of this prospective study is to examine the effects of maternal depression on the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy and its impact on variables related to neonatal outcome. This will be achieved by studying mood, plasma corticotropin releasing hormone (CRH), salivary cortisol, and neonatal outcome in the following groups of pregnant women: 1) 50 women with major depression who are depressed and not on antidepressants; 2) 50 women with a history of major depression who are treated with an SSRI and are euthymic; 3) 50 women without a history of major depression who are euthymic and not on antidepressants. Maternal mood state and anxiety will be assessed across each month of pregnancy; an assessment of HPA axis activity will be made in each trimester with measurements of plasma CRH and salivary cortisol. Neonatal outcome measures will include infant birth weight, gestational age, and performance on the Brazelton Neonatal Behavioral Assessment Scale. Information gained from this study will help clinicians and patients better understand the impact of untreated maternal depression versus treatment with antidepressants on HPA axis activity and the neonate and better assess the risks and benefits of treatment versus no medication during pregnancy. During the Award period, Dr. Suri will follow an organized program of inter- disciplinary training and supervised research under the sponsorship of Dr. Lori Altshuler. She will undergo coursework in endocrinology, physiology, embryology, neuroscience, biostatistics, and research design. She will complete a methodologically sound study of mood and endocrinology across pregnancy and effects on neonatal outcome. This research and career development plan will provide a foundation for future independent investigation regarding the management of psychiatric disorders during pregnancy.